GENERATION MECHANISMS AND SYNAPTIC GAINS FOR ABNORMAL BETA OSCILLATIONS IN THE BASAL GANGLIA

The network formed by the basal ganglia (BG), thalamus and cortex is critical for voluntary movement and movement disorders like Parkinson’s disease (PD). Neuronal activity in PD patients and animal models display exaggerated oscillatory synchronization in beta frequencies (12-30 Hz). Theoretical studies have proposed several potential mechanisms for the generation of abnormal beta oscillations. However, specific features such as frequency and power distribution across BG nuclei vary between patients and different animal models (rodents and non-human primates), making it difficult to confront theoretical models with experimental data and questioning whether the generation mechanism may differ across species.

We first use a model of the BG-thalamo-cortical network to evaluate the properties of oscillatory dynamics generated by each putative mechanism. The frequencies and coherence pattern of oscillations generated by one or several negative-feedback loops are derived in two different versions of the model with species-specific anatomical and physiological parameters, relying on rodent or primate data. These oscillatory properties can be compared with experimental observations.
Then, we aim to better constrain the model, in particular the synaptic gains between BG populations, relying on experiments combining electrophysiology and optogenetics. We compare responses of striatal, subthalamic and pallidal populations recorded during controlled activation of STN and striatal D2 neurons to the responses expected in the BG model. Using simulation-based inference, we determine the most likely set of synaptic gains in the network that best reproduce the experimental recordings.
Our results will improve the understanding of the mechanisms underlying beta activity in the BG-thalamo-cortical network.